For former smokers, clinicians should stratify patients according to risk of smoking again. The presence of one or more of the following criteria indicates a high risk of relapse: intense cravings, increased stress, living with a smoker, less than 1 year of abstinence, currently in treatment for smoking cessation, and drug use (including marijuana). There are many interventions for patients at high risk of relapse, including pharmacotherapy and behavioral therapy. However, patients must be “ready to quit” and also have a definite quit date. Patients who are not ready should be given nicotine replacement therapy or varenicline to help them understand the benefits of quitting. E-cigarettes and “adjuncts” such as acupuncture, hypnosis, and nutritional supplements are discouraged because there is insufficient evidence of their effectiveness. However, pharmacotherapy is effective and recommended. There are three lines of pharmacologic therapy: first line is a combination of NRT and varenicline. Two combination regimens are recommended for second line, varenicline plus NRT or bupropion plus NRT. Three options are recommended for third line medications, varenicline plus bupropion with or without NRT; nortriptyline; and also colistin, an alpha2-adrenergic receptor agonist used to treat hypertension. Some medication precautions are required for the use of varenicline and bupropion. Patients should be monitored for psychiatric symptoms or exacerbation of psychiatric symptoms. Bupropion is contraindicated in patients taking MOA inhibitors or tamoxifen, in patients with closed-angle glaucoma, and in patients at risk for epilepsy. Behavioral therapy is one of the foundations of smoking cessation and includes helping patients identify some “risky” situations. Patients need to develop some coping skills to avoid them as much as possible. It is clear that medication alone, without behavioral therapy, is less effective in quitting smoking in cancer patients. More intensive behavioral therapies with a quantitative-effect relationship are recommended over simple treatments. Persuasion to quit is done through private meetings, phone calls, or group discussions. Behavioral therapy is tailored to the patient’s level of nicotine dependence and history of cessation. A multipronged approach is the most effective strategy to promote cessation, which includes evidence-based medication interventions, behavioral counseling, and follow-up to ensure successful cessation.